A study on the correlation between MTHFR and folic acid combined with trace elements for the prevention of fetal malformations in the first trimester of pregnancy

This study aims to elucidate and examine the intricate interrelation between 5,10-methylenetetrahydrofolate reductase (MTHFR), combined folic acid (FA), and trace element supplementation as a preventive strategy against fetal malformations during the inaugural trimester of pregnancy. Eighty pregnant women selected from our hospital’s early obstetrics department from May 2021 to August 2021. Pregnant women are divided into the MTHFR combined group, FA, and trace element group. Comparing the basic data of patients, analyzing adverse reactions in pregnant women, and total birth risk situation, detecting MTHFR gene polymorphisms, and analyzing the correlation between MTHFR and FA in the prevention of fetal malformations in early pregnancy. Compared with the north, the southern region is more prone to FA deficiency. MTHFR degree of the MTHFR combined group was positively correlated with fetal malformations. The deformity rate was negatively correlated with FA and trace elements. Pregnant women in the first trimester may have fetal malformations, and the malformation rate is negatively correlated with FA and positively correlated with MTHFR level. Importantly, the inverse relationship between FA supplementation and malformation incidence underscores its significance as a preventive measure.


Introduction
[8] From a comprehensive analysis of regions, medical care, and economics, fetal deformities mainly occur in incompletely developed countries like China, accounting for more than three-quarters of cases. [9,10]ith the increasing ecological The trend of diversification and diversification of eating and drinking structure is gradually emerging.[13] Fetal deformities cause death and disability, which has become an important node affecting social stability.Therefore, it is particularly important to find a suitable low-risk method to prevent fetal malformations.
[16][17][18] Genetic susceptibility genes such as the MTHFR gene may be involved in the occurrence and development of fetal malformations. [17]Based on this foundation, this article takes women in early pregnancy as the starting point to study the value and correlation of MTHFR, FA, and trace elements in preventing fetal malformations, in order to provide reference for fetal assessment during pregnancy.The report is as follows.

Clinical data
The study was approved by the Ethics Committee of Wuhan Maternal and Child Health Hospital.The study enrolled a total of 80 participants from our institution between May 2021 and August 2021.These participants were evenly divided into 2 groups: the MTHFR combined group and the normal pregnant women group.Informed consent forms were duly signed by the legal guardians of preterm infants.Notably, there were no significant disparities in terms of age and gender among the selected patients (P > .05).Subsequently, we conducted a follow-up of discharged patients for a period of time.Further details are available in Table 1

Inclusion criteria
(1) Pregnant women are about 0 to 12 weeks away from delivery; (2) pregnant women aged 22 to 38 years old.

Exclusion criteria
(1) Cardio renal insufficiency and cancer patients should be excluded; (2) patients under the age of 18; (3) patients with genetic or mental illness; (4) patients without informed consent.

Detection methods
The human MTHFR gene was qualitatively detected.Four milliliter of fasting venous blood from all pregnant women and anticoagulation with EDTA for MTHFR gene testing.The polymorphism of MTHFR gene 677 T locus in the DNA of fresh whole blood samples was detected by fluorescent PCR.MTHFR 677 C/T gene detection kit was purchased from Shenzhen Osa Pharmaceutical Co., Ltd., Beijing, China, and the detection instrument was Light Cycler 480 fluorescence quantitative PCR instrument (Roche, Switzerland).Correlation analysis was performed using Spearman correlation analysis.

Statistical methods
Substitute the selected data into SPSS17.0software for data analysis, the measurement data is represented by (x ± s), and the t test is performed; the count data is represented by %, and the chi-square test is used.P < .05,there is statistical significance.

Adverse reactions in pregnant women
The adverse reactions of pregnant women in MTHFR combination group and normal pregnant women group are shown in Table 2.

Fetal birth risk situation
The normal pregnant women group was better than the MTHFR combined group (P < .05).Compared with the 2 groups, the low and high risk groups were both 0. There were 25 cases of fetal medium risk in the MTHFR combined group, but none were found in the normal pregnant women group.

Wuhan MTHFR gene polymorphism detection
The MTHFR genotype frequency and allele frequency distribution of Han women in Wuhan area were shown in Table 3.The frequency distribution of MTHFR gene in women in Wuhan has its own characteristics.

Lack of FA levels in the north and the south
Compared with the north, the southern region is more prone to FA deficiency (Table 4).

Age distribution of people at high risk of FA
People at high risk for FA are predominantly in the age range between 25 and 30 years (Fig. 1).

Correlation analysis between MTHFR and fetal malformations
Analysis (correlation) of MTHFR and fetal malformations with statistically significant differences between the MTHFR combination groups showed that the MTHFR degree of the MTHFR combined group was positively correlated with fetal malformations (R = 0.387, P = .253).

Correlation analysis between FA and fetal malformations
The analysis found that the amount of FA and fetal malformations were negatively distributed in the 2 groups (r = −0.517,P < .01).

Correlation analysis between trace elements and fetal malformations
Linear analysis showed that the level of trace elements was negatively correlated with fetal malformations (r = −0.383,P < .01).

Discussion
Fetal malformations arise from intricate causes, [19,20] encompassing maternal, fetal (hereditary), and environmental factors.23][24][25] It is particularly necessary to intervene in the early stages of pregnancy to improve the quality of the country's newborn population.[28][29] Folic acid plays a pivotal role in diverse methylation reactions involving amino acids and proteins.32][33] In this study, the selected subjects exhibit varying degrees of FA supplementation, contributing to a reduction in the risk of fetal malformations among pregnant women to a certain extent.
The primary limitation of this study centers on the relatively small sample size and the concentration of main clinical data within our hospital during the period of May to August 2021.Due to the large variety of trace elements, there is no specific correlation between trace elements and fetal malformation in early pregnancy.The future research endeavors will encompass an expanded sample collection from a broader range of sources and will encompass a multi-center study design.

The incidence of fetal malformations in early pregnancy
Pregnant women are in a state of mother-fetal community with multiple needs of nutrients, so the supply to pregnant women should be more than that of ordinary women.The average incidence of fetal malformations in pregnant women (12 weeks) found in domestic and foreign studies was 13.6%.
The pregnant women in this study were influenced by a convergence of multiple factors impacting fetal morphological development.

The effect of MTHFR on pregnant women
This analysis unveils a connection between FA and hemoglobin levels in early pregnancy, which could potentially lead to fetal malformation or miscarriage.MTHFR is associated with fetal malformations.Studies have shown that MTHFR gene mutation is an independent risk factor for fetal malformation.Correlation assessments of MTHFR gene polymorphism in the Wuhan region highlight distinct frequency distributions within local women.Thus, targeted regulation could mitigate the risk of congenital anomalies.

Effects of FA on pregnant women
In addition, the detection rate of fetal malformation in both groups was negatively correlated with the level of FA.Therefore, it is recommended that early pregnant women, especially those with anemia, supplement FA early to increase the fetal eugenic rate.

The effect of trace elements on pregnant women
Trace elements such as zinc, selenium, calcium, iron, copper, and magnesium are essential for the body, and even more so in the body of pregnancy.Studies underscore the pivotal role of trace elements (such as zinc, selenium, iron) in the onset of fetal malformations during early pregnancy.Zinc, implicated in the processing and synthesis of over 200 enzymes and proteins, stands as a pivotal component of cell mitosis, profoundly influencing the formation and progression of bodily organs.Inadequate zinc levels can severely compromise proper organ development, potentially leading to deformities.Similar significance is attributed to other trace elements, all of which wield substantial influence in the course of human growth.

Conclusion
In the early stages of pregnancy, pregnant women may experience fetal malformations, with the malformation rate being inversely correlated with folate levels and positively correlated with MTHFR levels.Trace elements serve as protective factors;  specifically, the more ample the trace element presence, the lower the likelihood of fetal malformations.Of course, the body is a multi-complex, and the study of nutrients alone fails to fully explain the rationale.Subsequent healthcare professionals should conduct comprehensive evaluations of maternal conditions.

Figure 1 .
Figure 1.Age distribution of people at high risk of folic acid.

Table 1
Compares the general data of the patients.

Table 3
Determination results of FAM and VTC gene polymorphism test in Wuhan region.

Table 4
Folic acid levels in the north and the south.